Hemolytic uremic syndrome (HUS) is a vascular disease with primary damage of the kidney in which glomerular microcapillaries become occluded with fibrin and platelets. Although HUS is associated with bacteria, viruses, immunosuppressants and AIDS, little is known about the mechanisms leading to the development of HUS. Most new information on HUS has come from studies related to the E. coli Shiga-like toxin (SLT)-producing dysentery bacteria and the subsequent appearance of HUS in those individuals. Our long-term goal is to describe, in biochemical terms, the mechanisms by which SLTs and host factors elicit the HUS disease state and to use this knowledge to develop effective preventive or therapeutic intervention modalities. The goal of the present study is to delineate the role of SLTs at the vascular endothelial cell level in the development of HUS. These studies utilize the human renal microvascular endothelial cell type which is believed to be the primary target of SLTs during the development of MUS. Our research plan seeks to answer why some endothelial cell types are more sensitive to the SLTs than are others and why human renal endothelial cells are particularly sensitive to SLT-2, as we recently demonstrated. The research plan is designed to examine the interaction of SLTs with endothelial cells under vascular flow conditions. A microchannel flow system is included which more closely represents the geometry, flow rate, and shear stress conditions of the kidney microvasculature where conditions of HUS occur. The contribution of flow parameters will be examined at the endothelial level for SLT binding and for subsequent effects on endothelial physiology. In summary, this research combines the areas of infectious disease and vascular physiology, and has as its primary goal to provide an understanding of the mechanisms underlying the development of renal vascular disease in HUS.